1. Field of the Invention
The present invention relates to novel anti-tumor compounds, methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are novel carbohydrate derivatives of paclitaxel that are more water soluble and have better biological properties compared to paclitaxel.
2. Background
Paclitaxel (Taxol.RTM.) is a chemotherapeutic agent that was originally
isolated from the bark of the Pacific yew, Taxus brevifolia. It has been shown to have antitumor activity toward a wide variety of cancers including breast, ovarian, melanoma, lung, colon, leukemias and others. Paclitaxel acts by promoting tubulin assembly and by stabilizing the microtubules to prevent their disassociation into free tubulin. Actively dividing cells are thus particularly sensitive to paclitaxel and become arrested at the G2/mitosis cell cycle transition.
Although paclitaxel has promising antitumor activity, it has been difficult to develop for clinical treatments due to its very low solubility in water. Paclitaxel is administered in large volume, low concentration formulations with Cremophor EL which results in many patients developing side effects such as hypersensitivity reactions. Thus, it would be extremely desirable to develop novel paclitaxel derivatives that have increased water solubility while maintaining or surpassing the cytotoxic activity of paclitaxel itself.
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